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Imaging with multiple modalities can maximise the information gained from the analysis of a single sample. probes for optical fluorescence and X-ray fluorescence microscopy based on brominated 4-amino-1,8-naphthalimide and BODIPY scaffolds have been successfully designed and synthesised. Herein we show that these prototype probes, based on each of these scaffolds, can be imaged in two different cancer cell lines, and that the respective optical fluorescence and X-ray fluorescence signals are well correlated in these images.

Abstract: Reactive oxygen species (ROS) are a by-product of the activity of cytochrome P450 steroidogenic enzymes. Antioxidant enzymes protect against ROS damage. To identify if any particular antioxidant enzyme is used to protect against ROS produced by granulosa cells as follicles enlarge and produce oestradiol, we measured in the bovine granulosa cells the expression of two steroidogenic enzymes (CYP11A1, CYP19A1), important for progesterone and oestradiol production. We also measured the expression of the members (FDXR, FDX1, POR) of their electron transport chains (ETC). We measured antioxidant enzymes (GPXs 1-8, CAT, SODs 1 and 2, PRDXs 1-6, GSR, TXN, TXNRDs 1-3). Since selenium is an active component of GPXs, the selenium-uptake receptors (LRPs 2 and 8) were measured. Only the selenium-dependent GPX1 showed the same increase in expression as the steroidogenic enzymes did with increasing follicle size. GPX4 and PRDX2/6 decreased with follicle size, whereas SOD1/2, CAT, GSR, and TXNRD3 were lowest at the intermediate sizes. The other antioxidant enzymes were unchanged or expressed at low levels. The expression of the selenium-uptake receptor LRP8 also increased significantly with follicle size. Correlation analysis revealed statistically significant and strongly positive correlations of the steroidogenic enzymes and their ETCs with both GPX1 and LRP8. These results demonstrate a relationship between the expression of genes involved in steroidogenesis and selenium-containing antioxidant defence mechanisms. They suggest that during the late stages of folliculogenesis, granulosa cells are dependent on sufficient expression of GPX1 and the selenium transporter LRP8 to counteract increasing ROS levels caused by the production of steroid hormones., Lay Summary: In the ovary, eggs are housed in follicles which contain the cells that produce oestrogen in the days leading up to ovulation of the egg. Oestrogen is produced by the action of enzymes. However, some of these enzymes also produce by-products called reactive oxygen species (ROS). These are harmful to eggs. Fortunately, cells have protective antioxidant enzymes that can neutralise ROS. This study was interested in which particular antioxidant enzyme(s) might be involved in neutralising the ROS in follicle cells. It was found that only one antioxidant enzyme, GPX1, appeared to be co-regulated with the enzymes that produce oestrogen and progesterone in the follicular cells. GPX1 contains the essential mineral selenium. In summary, this study has identified which antioxidant appears to be involved in neutralising ROS in the days leading to ovulation. It highlights the importance of selenium in the diet.

Background: Core lexicon (CL) analysis is a time efficient and possibly reliable measure that captures discourse production abilities. For people with aphasia, CL scores have demonstrated correlations with aphasia severity, as well as other discourse and linguistic measures. It was also found to be clinician-friendly and clinically sensitive enough to capture longitudinal changes in aphasia. To our knowledge, CL has never been investigated in individuals with neurologically progressive disease., Aims: As a preliminary investigation, we sought to investigate (1) whether CL scores correlate with dementia severity, (2) whether CL scores correlate with measures of discourse quality, and (3) whether CL scores correlate with other measures of lexical/semantic access., Methods & Procedures: Twelve participants with a cognitive impairment associated with dementia of the Alzheimer's type (DAT) completed several measures of language and cognitive ability, as well as provide a language sample from the wordless picture book, Picnic., Results & Conclusion: Results are informative, as they provide insight into characteristics of CL and provide support for potential use of CL in individuals with neurologically progressive disease. The results indicated that CL scores do correlate with dementia severity and several measures of language ability, indicating they may provide a useful measure of language abilities in DAT, but more research is needed., What This Paper Adds: What is already known on the subject Core lexicon (CL) analysis is an assessment measure of discourse ability, most closely related to informativeness or productivity, used in aphasiology that is easier to use and less time consuming than previous measures of informativeness, such as correct information units or type-token ratio (TTR). For people with aphasia, CL analysis correlates with aphasia severity, measures of informativeness, as well as other measures of discourse quality. It has also been shown to be faster and more reliable between scorers than other informativeness measures. What this study adds Core lexicon analysis is a new simple and online method for assessing the informativeness of a discourse sample without the need to record or transcribe the language sample. CL is receiving a lot of attention in aphasia, correlating with everything from aphasia severity to measures of productivity and lexical access, as well as measures of informativeness. Unfortunately, no one has investigated CL analysis in dementia. The study demonstrates the first evidence that CL analysis may be a useful measure for determining dementia severity and language quality in people with dementia. What are the clinical implications of this work? Core lexicon analysis may provide clinicians and researchers with an easy method for assessing the discourse of people with a cognitive impairment associated with dementia of the Alzheimer's type. This will improve initial assessment, as well as improve ongoing language assessment that may provide clues into their functional ability to communicate effectively., (© 2024 Royal College of Speech and Language Therapists.)

The tropical shrub Coelospermum decipiens (Rubiaceae) is an extreme selenium (Se) hyperaccumulator, reported to accumulate up to 1140 µg Se g-1 when found growing on soils with Se

Most nonoccupational human exposure to thallium (Tl) occurs via consumption of contaminated food crops. Brassica cultivars are common crops that can accumulate more than 500 μg Tl g -1 . Knowledge of Tl uptake and translocation mechanisms in Brassica cultivars is fundamental to developing methods to inhibit Tl uptake or conversely for potential use in phytoremediation of polluted soils. Brassica cultivars (25 in total) were subjected to Tl dosing to screen for Tl accumulation. Seven high Tl-accumulating varieties were selected for follow-up Tl dosing experiments. The highest Tl accumulating Brassica cultivars were analyzed by synchrotron-based micro-X-ray fluorescence to investigate the Tl distribution and synchrotron-based X-ray absorption near-edge structure spectroscopy (XANES) to unravel Tl chemical speciation. The cultivars exhibited different Tl tolerance and accumulation patterns with some reaching up to 8300 μg Tl g -1 . The translocation factors for all the cultivars were >1 with Brassica oleracea var. acephala (kale) having the highest translocation factor of 167. In this cultivar, Tl is preferentially localized in the venules toward the apex and along the foliar margins and in minute hot spots in the leaf blade. This study revealed through scanning electron microscopy and X-ray fluorescence analysis that highly Tl-enriched crystals occur in the stoma openings of the leaves. The finding is further validated by XANES spectra that show that Tl(I) dominates in the aqueous as well as in the solid form. The high accumulation of Tl in these Brassica crops has important implications for food safety and results of this study help to understand the mechanisms of Tl uptake and translocation in these crops.

Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation states, Cu2+ and Cu+in vitro, and supplemental Cu2+ has been shown to improve the fungicidal activity of the peptide against C. albicans in culture. However, the exact role of Cu on the antifungal activity of Hist-5 and whether direct peptide-Cu interactions occur intracellularly has yet to be fully determined. Here, we used a combination of fluorescence spectroscopy and confocal microscopy experiments to show reversible Cu-dependent quenching of a fluorescent Hist-5 analogue, Hist-5*, indicating a direct interaction between Hist-5 and intracellular Cu. X-ray fluorescence microscopy images revealed peptide-induced changes to cellular Cu distribution and cell-associated Cu content. These data support a model in which Hist-5 can facilitate the hyperaccumulation of Cu in C. albicans and directly interact with Cu intracellularly to increase the fungicidal activity of Hist-5., (© The Author(s) 2023. Published by Oxford University Press.)

Imaging techniques permit the study of the molecular interactions that underlie health and disease. Each imaging technique collects unique chemical information about the cellular environment. Multimodal imaging, using a single probe that can be detected by multiple imaging modalities, can maximise the information extracted from a single cellular sample by combining the results of different imaging techniques. Of particular interest in biological imaging is the combination of the specificity and sensitivity of optical fluorescence microscopy (OFM) with the quantitative and element-specific nature of X-ray fluorescence microscopy (XFM). Together, these techniques give a greater understanding of how native elements or therapeutics affect the cellular environment. This review focuses on recent studies where both techniques were used in conjunction to study cellular systems, demonstrating the breadth of biological models to which this combination of techniques can be applied and the potential for these techniques to unlock untapped knowledge of disease states.

Arsenic, in the simple form of arsenic trioxide, is currently marketed for the treatment of acute promyelocytic leukemia. Due to the multifaceted mechanisms of action of arsenic, it has also shown promise in other types of leukemias but is hindered by its toxic effects toward normal cells. This research has aimed to determine whether tumor-homing peptide complexes of arsenic can be designed and developed to strategically target specific cancers. The end goal is to achieve dose reduction and decreased side effects of the resultant arsenic therapeutic agent. In this article, we present the synthesis, characterization, and stability studies of a new class of As-peptide complexes designed to target leukemia. In vitro biological studies of the most stable complex show 1000 times greater toxicity toward leukemia cells over human blood cells, indicating potential for progression to in vivo studies.

Pityrogramma calomelanos and Pteris vittata are cosmopolitan fern species that are the strongest known arsenic (As) hyperaccumulators, with potential to be used in the remediation of arsenic-contaminated mine tailings. However, it is currently unknown what chemical processes lead to uptake of As in the roots. This information is critical to identify As-contaminated soils that can be phytoremediated, or to improve the phytoremediation process. Therefore, this study identified the in situ distribution of As in the root interface leading to uptake in P. calomelanos and P. vittata, using a combination of synchrotron micro-X-ray fluorescence spectroscopy and X-ray absorption near-edge structure imaging to reveal chemical transformations of arsenic in the rhizosphere-root interface of these ferns. The dominant form of As in soils was As(V), even in As(III)-dosed soils, and the major form in P. calomelanos roots was As(III), while it was As(V) in P. vittata roots. Arsenic was cycled from roots growing in As-rich soil to roots growing in control soil. This study combined novel analytical approaches to elucidate the As cycling in the rhizosphere and roots enabling insights for further application in phytotechnologies to remediated As-polluted soils., (© The Author(s) 2023. Published by Oxford University Press.)

Cognitive changes following adjuvant treatment for breast cancer (BC) are well documented following chemotherapy. However, limited studies have examined cognitive and/or language functions in chemotherapy-naive women with BC taking tamoxifen (TAM). Using ambulatory cognitive assessment, we investigated the trajectory of cognitive and language changes during early period of adjuvant endocrine treatment (TAM) in women with BC at two time periods (pretreatment and 2 months after treatment began). Four women with BC and 18 cognitively healthy age-matched controls completed three cognitive tasks using smartphones, during a short time period (5 days) and repeated them at two time periods. To determine language ability, language samples were collected at two time periods, where the participants described two stories from two wordless picture books and samples were assessed using core lexicon analyses. Wilcoxon-signed rank tests were computed to identify differences in linguistic and cognitive performances of both the groups at two time periods. No significant within-group or between-group differences were seen on the cognitive and language tasks at the two time periods; however, women with BC performed more poorly compared to the control group. We did see decline in some women with BC and not in others, in cognition and language during initial course of TAM treatment. However, the approach we used to assess these changes is valuable and innovative. This approach will help refine current research paradigms for determining cognitive and linguistic changes and will help determine if women with BC might require language intervention in the future., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Few studies have reported information related to the cost-effectiveness of traditional face-to-face treatments for aphasia. The emergence and demand for telepractice approaches to aphasia treatment has resulted in an urgent need to understand the costs and cost-benefits of this approach., Methods: Eighteen stroke survivors with aphasia completed community-based aphasia telerehabilitation treatment, utilizing the Language-Oriented Treatment (LOT) delivered via Webex videoconferencing program. Marginal benefits to treatment were calculated as the change in Western Aphasia Battery-Revised (WAB-R) score pre- and post-treatment and marginal cost of treatment was calculated as the relationship between change in WAB-R aphasia quotient (AQ) and the average cost per treatment. Controlling for demographic variables, Bayesian estimation evaluated the primary contributors to WAB-R change and assessed cost-effectiveness of treatment by aphasia type., Results: Thirteen out of 18 participants experienced significant improvement in WAB-R AQ following telerehabilitation delivered therapy. Compared to anomic aphasia (reference group), those with conduction aphasia had relatively similar levels of improvement whereas those with Broca's aphasia had smaller improvement. Those with global aphasia had the largest improvement. Each one-point of improvement cost between US$89 and US$864 for those who improved (mean = US$200) depending on aphasia type/severity., Discussion: Individuals with severe aphasia may have the greatest gains per unit cost from treatment. Both improvement magnitude and the cost per unit of improvement were driven by aphasia type, severity and race. Economies of scale to aphasia treatment-cost may be minimized by treating a variety of types of aphasia at various levels of severity.

Main Conclusion: Micro-analytical techniques to untangle Se distribution and chemical speciation in plants coupled with molecular biology analysis enable the deciphering of metabolic pathways responsible for Se tolerance and accumulation. Selenium (Se) is not essential for plants and is toxic at high concentrations. However, Se hyperaccumulator plants have evolved strategies to both tolerate and accumulate > 1000 µg Se g -1 DW in their living above-ground tissues. Given the complexity of the biochemistry of Se, various approaches have been adopted to study Se metabolism in plants. These include X-ray-based techniques for assessing distribution and chemical speciation of Se, and molecular biology techniques to identify genes implicated in Se uptake, transport, and assimilation. This review presents these techniques, synthesises the current state of knowledge on Se metabolism in plants, and highlights future directions for research into Se (hyper)accumulation and tolerance. We conclude that powerful insights may be gained from coupling information on the distribution and chemical speciation of Se to genome-scale studies to identify gene functions and molecular mechanisms that underpin Se tolerance and accumulation in these ecologically and biotechnologically important plants species. The study of Se metabolism is challenging and is a useful testbed for developing novel analytical approaches that are potentially more widely applicable to the study of the regulation of a wide range of metal(loid)s in hyperaccumulator plants., (© 2022. The Author(s).)

Although Alzheimer's disease (AD) was first described over a century ago, it remains the leading cause of age-related dementia. Innumerable changes have been linked to the pathology of AD; however, there remains much discord regarding which might be the initial cause of the disease. The "amyloid cascade hypothesis" proposes that the amyloid β (Aβ) peptide is central to disease pathology, which is supported by elevated Aβ levels in the brain before the development of symptoms and correlations of amyloid burden with cognitive impairment. The "metals hypothesis" proposes a role for metal ions such as iron, copper, and zinc in the pathology of AD, which is supported by the accumulation of these metals within amyloid plaques in the brain. Metals have been shown to induce aggregation of Aβ, and metal ion chelators have been shown to reverse this reaction in vitro . 8-Hydroxyquinoline-based chelators showed early promise as anti-Alzheimer's drugs. Both 5-chloro-7-iodo-8-hydroxyquinoline (CQ) and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2) underwent unsuccessful clinical trials for the treatment of AD. To gain insight into the mechanism of action of 8HQs, we have investigated the potential interaction of CQ, PBT2, and 5,7-dibromo-8-hydroxyquinoline (B2Q) with Cu(II)-bound Aβ(1-42) using X-ray absorption spectroscopy (XAS), high energy resolution fluorescence detected (HERFD) XAS, and electron paramagnetic resonance (EPR). By XAS, we found CQ and B2Q sequestered ∼83% of the Cu(II) from Aβ(1-42), whereas PBT2 sequestered only ∼59% of the Cu(II) from Aβ(1-42), suggesting that CQ and B2Q have a higher relative Cu(II) affinity than PBT2. From our EPR, it became clear that PBT2 sequestered Cu(II) from a heterogeneous mixture of Cu(II)Aβ(1-42) species in solution, leaving a single Cu(II)Aβ(1-42) species. It follows that the Cu(II) site in this Cu(II)Aβ(1-42) species is inaccessible to PBT2 and may be less solvent-exposed than in other Cu(II)Aβ(1-42) species. We found no evidence to suggest that these 8HQs form ternary complexes with Cu(II)Aβ(1-42).

Purpose: Core lexicon measures have received growing attention in research. They are intended to provide clinicians with a clinician-friendly means to quantify word retrieval ability in discourse based on normal expectations of discourse production for specific discourse elicitation tasks. To date, different criteria have been used to develop core lexicon measures by groups of researchers. The need for statistical guidance in pursuit of the psychologically robust measure has been recognized., Aims: This study was to investigate the best criterion for accurate measurement. Specifically, we focused on two criteria ( frequency vs. percentage ) that have previously been used for the development of core lexicon measures., Method: Core lexicon measures consisting of five different checklists by word class (verbs, nouns, adjectives, adverbs, and function words) and developed by the two criteria were applied to language samples produced by 470 cognitively healthy adults. Performance in word retrieval ability at the discourse level was modeled as a latent variable based on the observed proportions of the production of core lexicon items in two different sets of core lexicon measures using structural equation modeling., Results: Results indicated that both criterion for core lexicon measures capture word retrieval ability in discourse. Greater residual variances were found in the core lexicon measure established by the percentage criterion compared to the one established by the frequency criterion. This indicates that the measure based on the percentage criterion is more affected by measurement errors., Conclusions: The findings provide evidence that the frequency criterion is better to use for the development of core lexicon measures for core nouns, verbs, adjectives, and adverbs, but not for function words. However, our findings are limited to core lexicon measures based on language samples elicited by wordless picture books. This may not be easily applied to other core lexicon measures that use different discourse elicitation tasks due to the difference in quality and quantity of language samples. Ideally, the same approach should be replicated to evaluate the appropriateness of respective criteria in the development of core lexicon measures., Supplemental Material: https://doi.org/10.23641/asha.20304144.

Macadamia integrifolia and M. tetraphylla, unlike M. ternifolia, are known for their edible nuts. All three species over-accumulate the trace metal nutrient manganese (Mn) in their shoots. This study seeks to examine tissue- and cellular-level distribution of Mn and other plant nutrients in the three Macadamia species. The distribution of Mn, calcium, iron, and potassium were investigated in whole leaves and cross-sections of roots, petioles, and leaves using synchrotron-based X-ray fluorescence microscopy (XFM) in M. integrifolia, M. tetraphylla, and M. ternifolia. The results show Mn sequestration primarily in the leaf and midrib palisade mesophyll cells of all three species. Leaf interveinal regions, root cortical cells, and phloem cells were also found to be Mn loaded. The current study confirms earlier findings but further reveals that Mn is concentrated in the vacuoles of mesophyll cells owing to the exceptional resolution of the synchrotron XFM data, and the fact that fresh hydrated samples were used. New insights gained here into Mn compartmentalization in these highly Mn-tolerant Macadamias expand knowledge about potentially toxic over-accumulation of an essential micronutrient, which ultimately stands to inform strategies around farming edible species in particular., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Light verbs are highly frequent and semantically impoverished words. It is currently not known whether light verb production in discourse tasks differs by age or for people with dementia of the Alzheimer's type (DAT)., Aims: The purpose of the current study was two-fold: (1) to determine whether there is a relationship between age and the proportion of light verbs produce during a narrative discourse task; and (2) to determine whether people with DAT produce a different proportion of light verbs compared with neurotypical adults., Methods & Procedures: A total of 469 neurotypical adults and 12 participants with DAT produced narratives from a wordless picture book., Outcome & Results: The results indicated that light verb production increases as a function of age, even when controlling for education, and people with DAT produced a higher light verb-word ratio compared with neurotypical adults when matched for age and education., Conclusion & Implication: Light verb use may increase as a function of age due to declines in retrieval ability. These declines are not only more pronounced in people with DAT, but also semantic knowledge deficits may contribute to a reliance on light verbs., What This Paper Adds: Light verbs are typically some of the first verbs learned due to their simple semantic construction and high frequency. However, two things are unknown: (1) how light verbs changed across the adult lifespan; and (2) whether cognitive impairment changes light verb production. The study found that light verb production increases as a function of age, and that people with DAT used a higher ratio of light verbs to words in a narrative task compared with neurotypical adults. However, despite the findings, more research is needed to determine their clinical utility. Future research may wish to investigate whether light verbs (1) facilitate comprehension in older adults or (2) may be used in cognitive-linguistic assessments for cognitive impairments., (© 2022 Royal College of Speech and Language Therapists.)

The molecular biology and genetics of the Ni-Cd-Zn hyperaccumulator Noccaea caerulescens has been extensively studied, but no information is yet available on Ni and Zn redistribution and mobilization during seed germination. Due to the different physiological functions of these elements, and their associated transporter pathways, we expected differential tissue distribution and different modes of translocation of Ni and Zn during germination. This study used synchrotron X-ray fluorescence tomography techniques as well as planar elemental X-ray imaging to elucidate elemental (re)distribution at various stages of the germination process in contrasting accessions of N. caerulescens. The results show that Ni and Zn are both located primarily in the cotyledons of the emerging seedlings and Ni is highest in the ultramafic accessions (up to 0.15 wt%), whereas Zn is highest in the calamine accession (up to 600 μg g-1). The distribution of Ni and Zn in seeds was very similar, and neither element was translocated during germination. The Fe maps were especially useful to obtain spatial reference within the seeds, as it clearly marked the vasculature. This study shows how a multimodal combination of synchrotron techniques can be used to obtain powerful insights about the metal distribution in physically intact seeds and seedlings., (© The Author(s) 2022. Published by Oxford University Press.)

Globally, the majority of Ni hyperaccumulator plants occur on ultramafic soils in tropical regions, and the genus Phyllanthus, from the Phyllanthaceae family, is globally the most represented taxonomical group. Two species from Sabah (Malaysia) are remarkable because Phyllanthus balgooyi can attain >16 wt% of Ni in its phloem exudate, while Phyllanthus rufuschaneyi reaches foliar concentrations of up to 3.5 wt% Ni, which are amongst the most extreme concentrations of Ni in any plant tissue. Synchrotron X-ray fluorescence microscopy, nuclear microbe (micro-PIXE+BS) and (cryo) scanning electron microscopy with energy dispersive spectroscopy were used to spatially resolve the elemental distribution in the plant organs of P. balgooyi and P. rufuschaneyi. The results show that P. balgooyi has extraordinary enrichment of Ni in the (secondary) veins of the leaves, whereas in contrast, in P. rufuschaneyi Ni occurs in interveinal areas. In the roots and stems, Ni is localized mainly in the cortex and phloem but is much lower in the xylem. The findings of this study show that, even within the same genus, the distribution of nickel and other elements, and inferred processes involved with metal hyperaccumulation, can differ substantially between species., (© The Author(s) 2022. Published by Oxford University Press.)

Silver is commonly included in a range of household and medical items to provide bactericidal action. Despite this, the chemical fate of the metal in both mammalian and bacterial systems remains poorly understood. Here, we applied a metallomics approach using X-ray absorption spectroscopy (XAS) and size-exclusion chromatography hyphenated with inductively coupled plasma mass spectrometry (SEC-ICP-MS) to advance our understanding of the biochemical fate of silver ions in bacterial culture and cells, and the chemistry associated with these interactions. When silver ions were added to lysogeny broth, silver was exclusively associated with moderately-sized species (~30 kDa) and bound by thiolate ligands. In two representative bacterial pathogens cultured in lysogeny broth including sub-lethal concentrations of ionic silver, silver was found in cells to be predominantly coordinated by thiolate species. The silver biomacromolecule-binding profile in Staphylococcus aureus and Escherichia coli was complex, with silver bound by a range of species spanning from 20 kDa to >1220 kDa. In bacterial cells, silver was nonuniformly colocalised with copper-bound proteins, suggesting that cellular copper processing may, in part, confuse silver for nutrient copper. Notably, in the treated cells, silver was not detected bound to low molecular weight compounds such as glutathione or bacillithiol., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The photophysical and photochemical properties of two Pt(IV)Re(I) conjugates were studied via both experimental and computational methods. Both conjugates exhibit modest photocytotoxicity against ovarian cancer cells. X-ray fluorescence microscopy showed that Pt and Re colocalize in cells whether they had been irradiated or not. This work demonstrates the potential of photoactivated multilimetallic agents for combating cancer.

We report investigations on the anticancer activity of organometallic [M II/III (η 6 -p-cymene/η 5 -pentamethylcyclopentadienyl)] (M=Ru, Os, Rh, and Ir) complexes of N-heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono- or bidentate coordination via the NHC carbon atom or as N,C-donors. The metal complexes were investigated for their stability in aqueous solution, with the interpretation supported by density functional theory calculations, and reactivity to biomolecules. In vitro cytotoxicity studies suggested that the nature of both the metal center and the lipophilicity of the ligand determine the biological properties of this class of compounds. The Ir III complex 5 d bearing a benzimidazole-derived ligand was the most cytotoxic with an IC 50 value of 10 μM against NCI-H460 non-small cell lung carcinoma cells. Cell uptake and distribution studies using X-ray fluorescence microscopy revealed localization of 5 d in the cytoplasm of cancer cells., (© 2021 Wiley-VCH GmbH.)

Rapid Automatized Naming (RAN), a task in which participants must name a series of items as rapidly as possible, has been very useful as a measure of cognitive abilities that predict reading skill both in children and in young adults (YAs). This study examined RAN performance of 100 YAs and 80 cognitively healthy older adults (OAs). RAN performance was highly reliable but showed only a few weak correlations to other measures of individual differences used to study cognitive aging. RAN performance did not differ significantly by age group for symbolic RANs but was significantly slower for OAs than YAs for non-symbolic RANs. This pattern suggests that healthy aging is associated with little to no decline in the ability to sustain overlapping encoding and production of a sequence of items when it involves the form-to-form mapping required by symbolic RANs but with measurable decline in that ability when it involves the concept-to-form mapping required by non-symbolic RANs.

X-ray absorption spectroscopy and X-ray fluorescence microscopy are two synchrotron-based techniques frequently deployed either individually or in tandem to investigate the fates of metallodrugs and their biotransformation products in physiologically relevant sample material. These X-ray methods confer advantages over other analytical techniques in that they are nondestructive and require minimal chemical or physical manipulation of the sample before analysis, conserving both chemical and spatial information of the element(s) under investigation. In this review, we present selected examples of the use of X-ray absorption spectroscopy and X-ray fluorescence microscopy in studies of metallodrug speciation and localisation in vivo, in cell spheroids and in intact tissues and organs, and offer recent highlights in the advances of these techniques as they pertain to research on metallodrug action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim The aim of this scoping review is to identify the eye tracking paradigms and eye movement measures used to investigate auditory and reading comprehension deficits in persons with aphasia (PWA). Method MEDLINE via PubMed, Cochrane, CINAHL, Embase, PsycINFO, OTseeker, Scopus, Google Scholar, Grey Literature Database, and ProQuest Search (Dissertations & Theses) were searched for relevant studies. The Covidence software was used to manage the initial and full-text screening process for the search. Results and Discussion From a total of 1,803 studies, 68 studies were included for full-text screening. In addition, 418 records from gray literature were also screened. After full-text screening, 16 studies were included for this review-12 studies for auditory comprehension in PWA and four studies for reading comprehension in PWA. The review highlights the use of common eye tracking paradigms used to study language comprehension in PWA. We also discusse eye movement measures and how they help in assessing auditory and reading comprehension. Methodological challenges of using eye tracking are discussed. Conclusion The studies summarized in this scoping review provide evidence that the eye tracking methods are beneficial for studying auditory and reading comprehension in PWA.

The antibacterial properties of silver have been known for centuries and the threat of antibiotic-resistant bacteria has led to renewed focus on the noble metal. Silver is now commonly included in a range of household and medical items to imbue them with bactericidal properties. Despite this, the chemical fate of the metal in biological systems is poorly understood. Silver(I) is a soft metal with high affinity for soft donor atoms and displays much similarity to the chemistry of Cu(I). In bacteria, interaction of silver with the cell wall/membrane, DNA, and proteins and enzymes can lead to cell death. Additionally, the intracellular generation of reactive oxygen species by silver is posited to be a significant antimicrobial action. While the antibacterial action of silver is well known, bacteria found in silver mines display resistance against it through use of a protein ensemble thought to have been specifically developed for the metal, highlighting the need for judicious use. In mammals, ∼10-20% of ingested silver is retained by the body and thought to predominantly localize in the liver or kidneys. Chronic exposure can result in argyria, a condition characterized by blue staining of the skin, resulting from subdermal deposition of silver [as Ag(0)/sulfides], but more insidious side effects, such as inclusions in the brain, seizures, liver/kidney damage, and immunosuppression, have also been reported. Here, we hope to highlight the current understanding of the biological chemistry of silver and the necessity for continued study of these systems to fill existing gaps in knowledge., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although discourse-level assessments contribute to predicting real-world performance in persons with aphasia (PWA), the use of discourse measures is uncommon in clinical settings due to resource-heavy procedures. Moreover, assessing function word use in discourse requires the arduous procedure of defining grammatical categories for each word in language transcripts., Aims: The purpose of this exploratory study was twofold: (1) to develop core function word lists as a clinician-friendly means of evaluating function word use in discourse; and (2) to examine the ability of the core function word measure to differentiate PWA from cognitively healthy adults and persons with fluent aphasia from non-fluent aphasia., Methods & Procedures: The 25 most commonly used function words (core function words) were extracted from narrative language samples from 470 cognitively healthy adults, which were divided into seven age groups (20s, 30s, 40s, 50s, 60s, 70s and 80s). The percent agreement of core function words for 11 PWA (fluent aphasia = 5; non-fluent aphasia = 6) and 11 age- and education-matched controls were then calculated. Percent agreement for the core function words produced was compared between the controls and the PWA group, and between participants with fluent aphasia and non-fluent aphasia., Outcomes & Results: The results indicated that PWA produced fewer core function words from the lists than the control group, and that core function word use was strongly correlated with aphasia severity. Persons with non-fluent aphasia produced fewer core function words than those with fluent aphasia, although this could be a confound of aphasia classification from the use of the Western Aphasia Battery (WAB)-Revised., Conclusions & Implications: Core function word lists consisting of a limited number of items for quantifying function word use in discourse remain in a nascent stage of development. However, the findings are consistent with previous studies analysing the total production of function words in language samples produced by PWA. Therefore, core function words may potentially serve as a clinician-friendly manner of quantifying function words produced in discourse. What this paper adds What is already known on the subject Function word analysis in discourse requires arduous processes of identifying the error production and grammatical category of function words in discourse. Previous studies have demonstrated that core lexicon measures are an efficient, simple means of quantifying discourse in PWA. However, function words have never been considered for generating an independent core lexicon list. What this paper adds to existing knowledge As an exploratory study, we focused primarily on developing a clinician-friendly measure to evaluate function word production in discourse, motivated by the idea of an adaptation strategy within the core lexicon framework. Our findings demonstrated that by using a simple scoring system that the core lexicon measure provides, we differentiated the control group from the PWA group, and persons with fluent aphasia from persons with non-fluent aphasia. Additionally, we found significant correlations between function word production and aphasia severity determined by WAB Aphasia Quotient (AQ). What are the potential or actual clinical implications of this work? The results add empirical evidence for the utility of core function word lists for quantifying function word usage in discourse in PWA. Counting the presence and absence of function words in discourse will allow clinicians to avoid labour-intensive preparatory work, and to obtain useful diagnostic information in a less time-consuming way., (© 2020 Royal College of Speech and Language Therapists.)

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer's disease, and cancer. Two key 8HQs, CQ (5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (2-(dimethylamino)methyl-5,7-dichloro-8-hydroxyquinoline), have drawn considerable interest and have been the focus of many studies investigating their in vivo properties. These drugs have been described as copper and zinc ionophores because they do not cause metal depletion, as would be expected for a chelation mechanism, but rather cellular accumulation of these ions. In studies of their anti-cancer properties, CQ has been proposed to elicit toxic intracellular copper accumulation and to trigger apoptotic cancer cell death through several possible pathways. In this study we used synchrotron X-ray fluorescence imaging, in combination with biochemical assays and light microscopy, to investigate 8HQ-induced alterations to metal ion homeostasis, as well as cytotoxicity and cell death. We used the bromine fluorescence from a bromine labelled CQ congener (5,7-dibromo-8-hydroxyquinoline; B2Q) to trace the intracellular localization of B2Q following treatment and found that B2Q crosses the cell membrane. We also found that 8HQ co-treatment with Cu(ii) results in significantly increased intracellular copper and significant cytotoxicity compared with 8HQ treatments alone. PBT2 was found to be more cytotoxic, but a weaker Cu(ii) ionophore than other 8HQs. Moreover, treatment of cells with copper in the presence of CQ or B2Q resulted in copper accumulation in the nuclei, while PBT2-guided copper was distributed near to the cell membrane. These results suggest that PBT2 may be acting through a different mechanism than that of other 8HQs to cause the observed cytotoxicity.

PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) is a small Cu(II)-binding drug that has been investigated in the treatment of neurodegenerative diseases, namely, Alzheimer's disease (AD). PBT2 is thought to be highly effective at crossing the blood-brain barrier and has been proposed to exert anti-Alzheimer's effects through the modulation of metal ion concentrations in the brain, specifically the sequestration of Cu(II) from amyloid plaques. However, despite promising initial results in animal models and in clinical trials where PBT2 was shown to improve cognitive function, larger-scale clinical trials did not find PBT2 to have a significant effect on the amyloid plaque burden compared with controls. We propose that the results of these clinical trials likely point to a more complex mechanism of action for PBT2 other than simple Cu(II) sequestration. To this end, herein we have investigated the solution chemistry of Cu(II) coordination by PBT2 primarily using X-ray absorption spectroscopy (XAS), high-energy-resolution fluorescence-detected XAS, and electron paramagnetic resonance. We propose that a novel bis -PBT2 Cu(II) complex with asymmetric coordination may coexist in solution with a symmetric four-coordinate Cu(II)- bis -PBT2 complex distorted from coplanarity. Additionally, PBT2 is a more flexible ligand than other 8HQs because it can act as both a bidentate and a tridentate ligand as well as coordinate Cu(II) in both 1:1 and 2:1 PBT2/Cu(II) complexes.

Persons with traumatic brain injury (TBI) often present with discourse-level deficits that affect functional communication. These deficits are not thought to be primarily linguistic in nature but instead are thought to arise from the interaction of linguistic and cognitive processes. Discourse processing treatment (DPT) is a discourse-based treatment protocol which targets discourse deficits frequently seen in TBI. Attention Process Training-2 (APT-2) is a published treatment protocol which targets four levels of attention. The purpose of this article is to investigate the effectiveness of DPT and APT-2 in improving discourse production and cognition in adults with TBI. Our results suggest that DPT results in greater improvement in discourse informativeness and coherence, but the combination of DPT and APT-2 resulted in greater generalization to untrained stimuli. Both DPT and APT-2 appear to have some potential to improve cognition, but there was intersubject variability with regard to which treatment is more effective., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

8-Hydroxyquinolines (8HQs) are a family of lipophilic metal ion chelators that have been used in a range of analytical and pharmaceutical applications over the last 100 years. More recently, CQ (clioquinol; 5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) have undergone clinical trials for the treatment of Alzheimer's disease and Huntington's disease. Because CQ and PBT2 appear to redistribute metals into cells, these compounds have been redefined as copper and zinc ionophores. Despite the attention surrounding the clinical trials and the clear link between 8HQs and metals, the fundamental solution chemistry of how these compounds bind divalent metals such as copper and zinc, as well as their mechanism(s) of action in mammalian systems, remains poorly understood. In this study, we used a combination of X-ray absorption spectroscopy (XAS), high-energy resolution fluorescence detected (HERFD) XAS, electron paramagnetic resonance (EPR), and UV-visible absorption spectroscopies to investigate the aqueous solution chemistry of a range of 8HQ derivatives. To circumvent the known solubility issues with 8HQ compounds and their complexes with Cu(II), and to avoid the use of abiological organic solvents, we have devised a surfactant buffer system to investigate these Cu(II) complexes in aqueous solution. Our study comprises the first comprehensive investigation of the Cu(II) complexes formed with many 8HQs of interest in aqueous solution, and it provides the first structural information on some of these complexes. We find that halogen substitutions in 8HQ derivatives appear to have little effect on the Cu(II) coordination environment; 5,7-dihalogenated 8HQ conformers all have a pseudo square planar Cu(II) bound by two quinolin-8-olate anions, in agreement with previous studies. Conversely, substituents in the 2-position of the 8HQ moiety appear to cause significant distortions from the typical square-planar-like coordination of most Cu(II)-bis-8HQ complexes, such that the 8HQ moieties in the Cu(II)-bis-8HQ complex are rotated approximately 30-40° apart in a "propeller-like" arrangement.

Purpose: Comprehensive assessment of stuttering requires consideration of a wide range of behaviors that impact outcomes, and the Overall Assessment of the Speaker's Experience of Stuttering (OASES) is an assessment tool that accomplishes such. The purpose of this study was to determine how the individual components of the test contribute to the OASES' impact score., Method: Data collected at a university speech-language and hearing clinic from 29 adults were used for a relative weight analysis (RWA). RWA was utilized to determine the relative contributions of the OASES' subtests to the OASES' impact score. Confidence intervals for the individual relative weights were calculated for each OASES subtest and significance tests based on bootstrapping with 10,000 replications., Results: Differences were present in contributions of the OASES' subtests to the OASES' overall impact score, where the following explained a significant amount of variance in the OASES' impact score: Speaker's Reactions; Daily Communication; and Quality of Life. However, contribution of the subtest, "General Information", was not significant., Conclusion: Through examination of relative contributions to the impact of stuttering using the OASES, this project has identified differences in contributors to the overall impact of the disorder of stuttering. This information is beneficial to researchers and clinicians alike in that it gives specific guidance into what determines increased impact in adults who stutter (AWS). Future works should pursue clarification of these differences with an end goal of identifying and overcoming barriers to positive outcomes while also identifying and nurturing facilitators to optimal management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Thiones have been investigated as ligands in metal complexes with catalytic and biological activity. We report the synthesis, characterization, and biological evaluation of a series of M II/III complexes of the general formulae [M II (cym)(L)Cl]X (cym = η 6 - p -cymene) or [M III (Cp*)(L)Cl]X (Cp* = η 5 -pentamethylcyclopentadienyl), where X = Cl - or PF 6 - , and L represents heterocyclic derivatives of thiourea. The thiones feature a benzyl-triazolyl pendant and they act as bidentate ligands via N , S -coordination to the metal centers. Several derivatives have been investigated by single-crystal X-ray diffraction analysis. NMR investigations showed a counterion-dependent shift of several protons due to the interaction with the counterions. These NMR investigations were complemented with X-ray diffraction analysis data and the effects of different counterions on the secondary coordination sphere were also investigated by DFT calculations. In biological studies, the Ir benzimidazole derivative was found to accumulate in the cytoplasm and it was the most cytotoxic derivative investigated.

The complex fac-[Re(CO)3(dmphen)(para-tolylisonitrile)]+ (TRIP), where dmphen = 2,9-dimethyl-1,10-phenanthroline, is an endoplasmic reticulum stress-inducing anticancer agent (A. P. King, S. C. Marker, R. V. Swanda, J. J. Woods, S.-B. Qian and J. J. Wilson, Chem. - Eur. J., 2019, 25, 9206-9210). A second-generation compound fac-[Re(CO)3(dmphen)(para-iodobenzeneisonitrile)]+ (I-TRIP) was synthesized, and its intracellular distribution was investigated using X-ray fluorescence microscopy to show that these complexes are highly stable in vitro.

Three metallophyte species, Persicaria capitata, P. puncata (Polygonaceae), Conyza cordata (Asteraceae) from mineral wastes in the Zambian copper-cobalt belt were studied. This study focused on the elemental distribution in the roots, stems and leaves, using a range of techniques: micro-PIXE, SEM-EDS synchrotron XFM and XAS. The species differed in their responses to growing on Co-Cu-enriched soils: Persicaria puncata is a Co hyperaccumulator (up to 1060 μg g-1 in leaves), while Persicaria capitata and Conyza cordata are Co-excluders. All three species are Cu-accumulators. The highest concentrations of Cu-Co are in the epidermal cells, whereas in Persicaria puncata Co was also enriched in the phloem. The Co coordination chemistry shows that an aqueous Co(ii)-tartrate complex was the predominant component identified in all plants and tissues, along with a minor component of a Co(iii) compound with oxygen donor ligands. For Cu, there was considerable variation in the Cu speciation in the various tissues and across the three species. In contrast to hyperaccumulator plants, excluder and accumulator type plants have received far less attention. This study highlights the different biopathways of transition elements (Cu, Co) in hyper-tolerant plant species showing different responses to metalliferous environments.

The mitochondrial calcium uniporter (MCU) is the ion channel that mediates Ca 2+ uptake in mitochondria. Inhibitors of the MCU are valuable as potential therapeutic agents and tools to study mitochondrial Ca 2+ . The best-known inhibitor of the MCU is the ruthenium compound Ru360. Although this compound is effective in permeabilized cells, it does not work in intact biological systems. We have recently reported the synthesis and characterization of Ru265, a complex that selectively inhibits the MCU in intact cells. Here, the physical and biological properties of Ru265 and Ru360 are described in detail. Using atomic absorption spectroscopy and X-ray fluorescence imaging, we show that Ru265 is transported by organic cation transporter 3 (OCT3) and taken up more effectively than Ru360. As an explanation for the poor cell uptake of Ru360, we show that Ru360 is deactivated by biological reductants. These data highlight how structural modifications in metal complexes can have profound effects on their biological activities., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selenium (Se), a trace element essential for human and animal biological processes, is deficient in many agricultural soils. Some extremely rare plants can naturally accumulate extraordinarily high concentrations of Se. The native legume Neptunia amplexicaulis, endemic to a small area near Richmond and Hughenden in Central Queensland, Australia, is one of the strongest Se hyperaccumulators known on Earth, with foliar concentrations in excess of 4000 μg Se g -1 previously recorded. Here, we report on the Se distribution at a whole plant level using laboratory micro X-ray Fluorescence Microscopy (μXRF) and scanning electron microscopy (SEM-EDS), as well as on chemical forms of Se in various tissues using liquid chromatography-mass spectrometry (LC-MS) and synchrotron X-ray absorption spectroscopy (XAS). The results show that Se occurs in the forms of methyl-selenocysteine and seleno-methionine in the foliar tissues, with up to 13 600 μg Se g -1 total in young leaves. Selenium was found to accumulate primarily in the young leaves, flowers, pods and taproot, with lower concentrations present in the fine-roots and stem and the lowest present in the oldest leaves. Trichomes were not found to accumulate Se. We postulate that Se is (re)distributed in this plant via the phloem from older leaves to newer leaves, using the taproot as the main storage organ. High concentrations of Se in the nodes (pulvini) indicate this structure may play an important a role in Se (re)distribution. The overall pattern of Se distribution was similar in a non-Se tolerant closely related species (Neptunia gracilis), although the prevailing Se concentrations were substantially lower than in N. amplexicaulis.